Since one enantiomer of an asymmetric compound can differ from another enantiomer of that asymmetric compound in its actions within a living body, methods capable of providing optical resolution of enantiomeric mixtures as well as asymmetric synthesis methods have been considered important in organic chemistry.
Generally, compounds represented by Formula (1) set forth hereinbelow, are highly reactive and at the same time possess a unique chemical reactivity, because of strain associated with the three-membered ether ring. Various chemical conversions of the Formula (1) compounds are possible through ring opening reactions, and therefore, these compounds are important intermediates in the synthesis of organic compounds, and are also important as monomers in forming epoxy resins.
Stereoisomers of aliphatic epoxides can be used as raw materials in the synthesis of various compounds. Accordingly, if they could be analyzed, and also produced through a process that could be easily carried out on an industrial scale, a great contribution to the chemical arts would be made.
As conventional processes for obtaining optically active compounds, there are asymmetric synthesis methods, optical resolution methods by way of a diastereomer, and biochemical synthesis methods using an enzyme of a microorganism. Asymmetric synthesis processes have a drawback in that an intended compound having a high optical purity usually cannot be obtained. Similarly, processes which proceed by way of a diastereomer are difficult and equimolar amounts of different optically active compounds are necessary. Furthermore, biochemical synthesis processes are inadequate in that it is often quite difficult to find an appropriate enzyme or microorganism capable of achieving a desired synthesis.
A chiral separation of an aliphatic epoxide using a derivatized cyclodextrin as a chiral stationary phase (CSP) for a capillary gas chromatography column was reported by Professor Armstrong in Anal. Chem., 1990, Volume 62, pp. 914-923 and in A Guide to Using Cyclodextrin Bonded Phases for Gas Chromatography, (1990 Edition), Astec Co. However, these methods did not provide a good separation that could be used for a trace analysis of one of the enantiomers. In addition, gas chromatography methods are only suitable for analytical purposes, instead of being applicable to the preparation of stereoisomers.
On the contrary, liquid and supercritical fluid based chromatography methods can be used for both analytical purposes and the preparation of stereoisomers. There were a few separations of esters of epoxy higher fatty acids reported in the Journal of Chromatography, Biomedical Applications, Vol. 583, No. 2, pp. 231-235 (1992), and Anal. Biochem., Vol. 182, No. 2, pp. 300-303 (1989). However, of known liquid (and supercritical fluid) chromatographic CSPs, no one has previously reported to be able to separate stereoisomers of an aliphatic epoxide which has two or less attractive interaction points for hydrogen bonding, because such stereoisomers, whose difference is only based on the three dimensional structural difference, were heretofore believed to possess too little functionality to be enanitiomerically separated. In contrast, it is easy to recognize chirality if there exists three or more attractive interaction points for hydrogen bonding-like in the epoxy esters or epoxy acids illustrated immediately below. In this regard, three attractive interaction points (i.e., oxygen atoms) are available in such esters and acids for an attractive interaction, e.g., with a chiral stationary phase. ##STR1##
In the above illustrated epoxy esters and acids, the "dotted lines", indicate the presence of hydrogen bonding between oxygen atoms in the epoxy esters and acids and other molecules (e.g., in a chiral stationary phase).